He Wei, McConnell George C, Bellamkonda Ravi V
Neurological Biomaterials and Therapeutics, Wallace H Coulter Department of Biomedical Engineering, Georgia Institute of Technology/Emory University, 313 Ferst Drive, Atlanta, GA 30332, USA.
J Neural Eng. 2006 Dec;3(4):316-26. doi: 10.1088/1741-2560/3/4/009. Epub 2006 Nov 15.
Neural electrodes could significantly enhance the quality of life for patients with sensory and/or motor deficits as well as improve our understanding of brain functions. However, long-term electrical connectivity between neural tissue and recording sites is compromised by the development of astroglial scar around the recording probes. In this study we investigate the effect of a nanoscale laminin (LN) coating on Si-based neural probes on chronic cortical tissue reaction in a rat model. Tissue reaction was evaluated after 1 day, 1 week, and 4 weeks post-implant for coated and uncoated probes using immunohistochemical techniques to evaluate activated microglia/macrophages (ED-1), astrocytes (GFAP) and neurons (NeuN). The coating did not have an observable effect on neuronal density or proximity to the electrode surface. However, the response of microglia/macrophages and astrocytes was altered by the coating. One day post-implant, we observed an approximately 60% increase in ED-1 expression near LN-coated probe sites compared with control uncoated probe sites. Four weeks post-implant, we observed an approximately 20% reduction in ED-1 expression along with an approximately 50% reduction in GFAP expression at coated relative to uncoated probe sites. These results suggest that LN has a stimulatory effect on early microglia activation, accelerating the phagocytic function of these cells. This hypothesis is further supported by the increased mRNA expression of several pro-inflammatory cytokines (TNF-alpha, IL-1 and IL-6) in cultured microglia on LN-bound Si substrates. LN immunostaining of coated probes immediately after insertion and retrieval demonstrates that the coating integrity is not compromised by the shear force during insertion. We speculate, based on these encouraging results, that LN coating of Si neural probes could potentially improve chronic neural recordings through dispersion of the astroglial scar.
神经电极可以显著提高感觉和/或运动功能障碍患者的生活质量，并增进我们对脑功能的理解。然而，神经组织与记录位点之间的长期电连接会因记录探针周围星形胶质瘢痕的形成而受损。在本研究中，我们在大鼠模型中研究了基于硅的神经探针上的纳米级层粘连蛋白（LN）涂层对慢性皮质组织反应的影响。使用免疫组织化学技术评估活化的小胶质细胞/巨噬细胞（ED-1）、星形胶质细胞（GFAP）和神经元（NeuN），在植入涂层和未涂层探针后的1天、1周和4周评估组织反应。该涂层对神经元密度或与电极表面的接近程度没有明显影响。然而，涂层改变了小胶质细胞/巨噬细胞和星形胶质细胞的反应。植入后1天，与未涂层的对照探针位点相比，我们观察到LN涂层探针位点附近的ED-1表达增加了约60%。植入后4周，与未涂层探针位点相比，我们观察到涂层处的ED-1表达降低了约20%，同时GFAP表达降低了约50%。这些结果表明，LN对早期小胶质细胞活化具有刺激作用，加速了这些细胞的吞噬功能。培养的小胶质细胞在与LN结合的硅基质上几种促炎细胞因子（TNF-α、IL-1和IL-6）的mRNA表达增加进一步支持了这一假设。插入和取出后立即对涂层探针进行LN免疫染色表明，涂层完整性在插入过程中不受剪切力的影响。基于这些令人鼓舞的结果，我们推测，硅神经探针的LN涂层可能通过星形胶质瘢痕的分散来潜在地改善慢性神经记录。
